4.3 Article

Serum cytokine profiles predict outcomes of chronic hepatitis B patients discontinuing entecavir or tenofovir therapy

Journal

JOURNAL OF THE FORMOSAN MEDICAL ASSOCIATION
Volume 122, Issue 7, Pages 564-573

Publisher

ELSEVIER TAIWAN
DOI: 10.1016/j.jfma.2023.02.002

Keywords

Chronic hepatitis B; Nucleos(t)ide analogue; Antiviral therapy; Hepatitis flare; Cytokine

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Distinct hepatitis relapse has been observed after discontinuing ETV or TDF therapy in CHB patients. Serum cytokines at the end of therapy can be used for outcome prediction. Age, HBsAg levels at EOT, and certain cytokine levels were found to be predictive of virological and clinical relapse.
Background/purpose: Distinct hepatitis relapse has been observed after discontinuing enteca-vir (ETV) or tenofovir disoproxil fumarate (TDF) therapy in chronic hepatitis B (CHB) patients. End-of-therapy (EOT) serum cytokines were compared and used for outcome prediction.Methods: A total of 80 non-cirrhotic CHB patients in a tertiary medical center in Taiwan who discontinued ETV (n = 51) or TDF (n = 29) therapy after fulfilling the APASL guidelines were prospectively enrolled. Serum cytokines were measured at EOT and 3rd month afterwards. Multivariable analysis was performed to predict virological relapse (VR, HBV DNA >2000 IU/ mL), clinical relapse (CR, VR and alanine aminotransferase > 2-fold upper limit of normal) and hepatitis B surface antigen (HBsAg) seroclearance.Results: Compared with TDF group, ETV stoppers had greater interleukin 5 (IL-5), IL-12 p70, IL-13, IL-17 A and tumor necrosis factor alpha (TNF-alpha) (all P < 0.05) at EOT. Older age, TDF use, higher EOT HBsAg and IL-18 (Hazard ratio [HR], 1.01; 95% CI, 1.00-1.02) levels at EOT pre-dicted VR, while older age, higher EOT HBsAg and IL-7 (HR, 1.25; 95% CI, 1.00-1.56) levels pre-dicted CR. In TDF stoppers, higher IL-7 (HR, 1.29; 95% CI, 1.05-1.60) and IL-18 (HR, 1.02; 95% CI, 1.00-1.04) levels predicted VR, while IL-7 (HR, 1.34; 95% CI, 1.08-1.65) and interferon-gamma (IFN-gamma) (HR, 1.08; 95% CI, 1.02-1.14) levels predicted CR. A lower EOT HBsAg

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